Objective. To explore the mechanism of action of Bu-Fei-Yi-Shen formula (BFYSF) in treating chronic obstructive pulmonary disease (COPD) based on network pharmacology analysis and molecular docking validation. Methods. First of all, the pharmacologically active ingredients and corresponding targets in BFYSF were mined by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the analysis platform, and literature review. Subsequently, the COPD-related targets (including the pathogenic targets and known therapeutic targets) were identified through the TTD, CTD, DisGeNet, and GeneCards databases. Thereafter, Cytoscape was employed to construct the candidate component-target network of BFYSF in the treatment of COPD. Moreover, the cytoHubba plug-in was utilized to calculate the topological parameters of nodes in the network; then, the core components and core targets of BFYSF in the treatment of COPD were extracted according to the degree value (greater than or equal to the median degree values for all nodes in the network) to construct the core network. Further, the Autodock vina software was adopted for molecular docking study on the core active ingredients and core targets, so as to verify the above-mentioned network pharmacology analysis results. Finally, the Omicshare database was applied in enrichment analysis of the biological functions of core targets and the involved signaling pathways. Results. In the core component-target network of BFYSF in treating COPD, there were 30 active ingredients and 37 core targets. Enrichment analysis suggested that these 37 core targets were mainly involved in the regulation of biological functions, such as response to biological and chemical stimuli, multiple cellular life processes, immunity, and metabolism. Besides, multiple pathways, including IL-17, Toll-like receptor (TLR), TNF, and HIF-1, played certain roles in the effect of BFYSF on treating COPD. Conclusion. BFYSF can treat COPD through the multicomponent, multitarget, and multipathway synergistic network, which provides basic data for intensively exploring the mechanism of action of BFYSF in treating COPD.

Purpose: To investigate the anti-inflammatory effect of Bufei yishen formula on chronic obstructive pulmonary disease (COPD) and klotho expression in cigarette smoke extract (CSE)-treated BEAS-2B cells. Methods: Cigarette smoke extract (CSE) was diluted in Dulbecco's modified Eagle's medium (DMEM) and used to treat a COPD cell model established using BEAS-2B cells. The CSE-treated cells were transfected with klotho overexpression plasmid, and the COPD cell model was treated with Bufei yishen formula. Dexamethasone was used as positive control. Changes in the expressions of klotho, RIG-I, and NF-ĸB were determined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, while enzyme linked immunosorbent assay (ELISA) was used to evaluate changes in the expressions of IL-6 and TNF-α. Results: Klotho expression level was reduced in COPD model. Overexpression of klotho inhibited the expressions of IL-6, TNF-α, RIG-I, NF-κB, but bufei yishen formula increased klotho expression level and decreased the expressions of RIG-I, NF-κB, IL-6 and TNF-α. However, after CSE treatment, the anti-inflammatory effect of the formula decreased significantly when klotho expression was knocked down. Conclusion: Bufei yishen formula possesses anti-inflammatory effects which are significantly decreased after klotho knockdown. This suggests that the formula probably acts by upregulating klotho expression, thereby down-regulating the expressions of IL-6 and TNF-α via RIG-I/NF-κB pathway.

Background Bufei Yishen formula (BYF) is an effective prescription for the clinical treatment of chronic obstructive pulmonary disease (COPD). However, the molecular mechanism by which it exerts its pharmacological effects remains to be explored. Methods The human bronchial cell line BEAS-2B was treated with cigarette smoke extract (CSE). Cellular senescence markers were detected by Western blot and ELISA. Potential transcription factor of klotho was predicted using JASPAR and USCS databases. Results CSE induced cellular senescence with intracellular accumulation of cellular senescence biomarkers (p16, p21 and p27) and increased secretion of senescence-related secretory phenotypic (SASP) factors (IL-6, IL-8, and CCL3). In contrast, BYF treatment inhibited CSE-induced cellular senescence. CSE suppressed the transcription, expression and secretion of klotho, whereas BYF treatment rescued its transcription, expression and secretion. CSE downregulated the protein level of ZNF263, whereas BYF treatment rescued the expression of ZNF263. Furthermore, ZNF263-overexpressing BEAS-2B cells could inhibit CSE-induced cellular senescence and SASP factor secretion by upregulating the expression of klotho. Conclusion This study revealed a novel pharmacological mechanism by which BYF alleviates clinical symptoms of COPD patients, and regulating ZNF263 and klotho expression may be beneficial to the treatment and prevention of COPD.

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